Toluene → HCID 89714767, compound

Participants

Reaction Steps

130 mg (316 μmol) of 4-(4-aminophenyl)-6-ethyl-8,8-dimethyl-2-((S)-3-methylmorpholin-4-yl)-7,8-dihydro-6H-9-oxa-1,3,6-triazabenzocyclohepten-5-one suspended in 3 ml of dioxane are heated at 50° C. for 30 minutes in the presence of 233 μl of a 1.9 M solution of phosgene in toluene (442.3 mmol) and 75 μl (442.3 mmol) of DIEA. 391 mg (1.58 mmol) of (4-aminophenyl)-(4-dimethylaminopiperidin-1-yl)methanone are then added. The medium is stirred for 16 hours at room temperature. The mixture is evaporated under reduced pressure and the residue is taken up in water and extracted with DCM. The organic phase is washed twice with water, dried over MgSO4 and then filtered. The filtrate is evaporated under reduced pressure and the residue is then chromatographed on silica gel, eluting with a DCM/MeOH mixture from (100/0 v/v) up to (93/7 v/v). The product obtained is dissolved in a minimum amount of DCM and then reprecipitated from Et2O to give 61 mg of 1-[4-(4-dimethylaminopiperidine-1-carbonyl)phenyl]-3-{4-[6-ethyl-8,8-dimethyl-2-((S)-3-methylmorpholin-4-yl)-5-oxo-5,6,7,8-tetrahydro-9-oxa-1,3,6-triazabenzocyclohepten-4-yl]phenyl}urea.

Provenance & Evidence